David, SA and Awasthi, SK and Wiese, A and Ulmer, AJ and Lindner, B and Brandenburg, K and Seydel, U and Rietschel, ETh and Sonesson, A and Balaram, Padmanabhan (1996) Characterization of the interactions of a polycationic, amphiphilic, terminally branched oligopeptide with lipid A and lipopolysaccharide from the deep rough mutant of Salmonella minnesota. In: Journal of Endotoxin Research, 3 (5). 369 -379.
267.pdf - Published Version
Restricted to Registered users only
Download (5Mb) | Request a copy
The lipid A and lipopolysaccharide (LPS) binding and neutralizing activities of a synthetic, polycationic, amphiphilic peptide were studied. The branched peptide, designed as a functional analog of polymyxin B, has a six residue hydrophobic sequence, bearing at its N-terminus a penultimate lysine residue whose alpha- and epsilon-amino groups are coupled to two terminal lysine residues. In fluorescence spectroscopic studies designed to examine relative affinities of binding to the toxin, neutralization of surface charge and fluidization of the acyl domains, the peptide was active, closely resembling the effects of polymyxin B and its nonapeptide derivative; however, the synthetic peptide does not induce phase transitions in LPS aggregates as do polymyxin B and polymyxin B nonapeptide. The peptide was also comparable with polymyxin B in its ability to inhibit LPS-mediated IL-l and IL-6 release from human peripheral blood mononuclear cells. The synthetic compound is devoid of antibacterial activities and did not induce conductance fluxes in LPS-containing asymmetric planar membranes. These results strengthen the premise that basicity and amphiphilicity are necessary and sufficient physical properties that ascribe endotoxin binding and neutralizing activities, and further suggest that antibacterial/membrane perturbant and LPS neutralizing activities are dissociable, which may be of value in designing LPS-sequestering agents of low toxicity.
|Item Type:||Journal Article|
|Additional Information:||Copright of this article belongs to Sage Publications.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||03 Jun 2010 08:32|
|Last Modified:||19 Sep 2010 06:00|
Actions (login required)